A Study to Investigate Evoked Potentials as Markers of Ketamine-induced Cortical Plasticity in Patients With Major Depressive Disorder

Major Depressive Disorder Clinical Trial

Official title:

An Open-Label and Double-Blind Study to Investigate Evoked Potentials as Markers of Ketamine-induced Cortical Plasticity in Subjects With Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01957410
• Other study ID #: CR102607
• Secondary ID: KETIVTRD2004
• Status: Completed
• Phase: Phase 2
• First received: September 30, 2013
• Last updated: January 7, 2016
• Start date: February 2014
• Est. completion date: September 2015

Study information

• Verified date: January 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To evaluate if somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) obtained with electroencephalography (EEG) and electromyography (EMG) can be used to detect changes in cortical plasticity in responders to a single IV infusion of ketamine as compared to non-responders.

Description:

This study will be conducted in patients with Major Depressive Disorder (MDD) and divided into 2 sequential cohorts. Cohort 1 will be conducted in 12 patients at a single center. For each patient, there will be up to 4 sequential phases: a screening phase of up to 6 weeks, an open-label treatment phase of up to 4 weeks, an optional open-label treatment phase of up to 1 week, and a follow-up phase of up to 1 week (if applicable). Cohort 2 will be conducted in 20 patients and will be a multicenter, double-blind (neither physician nor patient knows the treatment that the patient receives), randomized (the study drug is assigned by chance), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) design. For each patient, there will be up to 4 sequential phases: a screening phase of up to 6 weeks, a double-blind treatment phase of up to 4 weeks, an optional open-label treatment phase of up to 1 week, and a follow-up phase of up to 1 week (if applicable). The total study duration for each patient will be maximally about 12 weeks. Participant safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Patient must be medically stable

• Patient must meet Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI)

• Patient must have had an inadequate response to at least 2 antidepressants, one of which is in the current episode of depression

• Patient must have an Inventory of Depressive Symptomatology 30-item Clinician-rated (IDS-C30) total score = 34 at Screening and Day -1

• Women must be postmenopausal, surgically sterile, or, if heterosexually active, practicing a highly effective method of birth control

• Men who are heterosexually active with a woman of childbearing potential must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:

• Patient has current signs and/or symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances

• Patient has a primary DSM-IV diagnosis of current (active) generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), anorexia nervosa, or bulimia nervosa

• Patient has a current diagnosis of bipolar disorder, mental retardation, or cluster b personality disorder (e.g., borderline personality disorders, antisocial personality disorder, etc)

• Patient has a current or prior diagnosis of a psychotic disorder or MDD with psychosis

• Patient has not responded to treatment with electroconvulsive therapy (ECT) in the current episode of depression

• Patient has suicidal ideation with intent to act, or has homicidal ideation/intent, during Screening phase per Investigator's clinical judgment

• Patient has any significant primary sleep disorder

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Ketamine
During Cohorts 1 and 2, a single ketamine 0.5 mg/kg dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. The predefined dose and infusion rate/duration should not be adjusted. If a patient is unable to tolerate the study medication, the infusion should be stopped. Within 1 week of completion of the open-label treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.
• Placebo
During Cohort 2, a single placebo dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. Within 1 week of completion of the double-blind treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of change from baseline to 4 hr post-dose on Day 1 in somatosensory evoked potential amplitudes (SEPs) between ketamine responders and ketamine non-responders.	SEPs are the electrical signals generated by the nervous system in response to somatosensory stimuli - typically through electrical stimulation of the median nerve. SEPs are read on the skull with electroencephalography (EEG). SEPs will be carried out as described by Cornwell and colleagues (Cornwell 2012) with the exception that instead of using magnetoencephalography SEPs will be recorded using a 64-channel EEG system. Identical procedures will be employed prior to and after study drug administration.	Baseline and 4 hours post-dose on Day 1	No
Primary	Comparison of change from baseline to 4 hr post-dose on Day 1 in motor evoked potential amplitudes (MEPs) between ketamine responders and ketamine non-responders.	MEPs are generated when stimulation of the brain on the motor cortex (with Transcranial Magnetic Stimulation [TMS], for example) causes the spinal cord and peripheral muscles to produce neuroelectrical signals. MEPs are typically measured in the hand muscles. The Motor Evoked Response to Transcranial Magnetic Stimulation (TMS MEPs) is being evaluated in this study at baseline and regularly after study drug administration. TMS MEPs will be assessed as described by Di Lazzaro and colleagues (Di Lazzaro 2003). A figure-of-eight coil will be held over the right motor cortex at the optimum scalp position to elicit motor responses in the contralateral first dorsal interosseus (FDI).	Baseline and 4 hours post-dose on Day 1	No